The specific aims of our studies are: 1) To define methods (with an emphasis on genetic recombination) for the production of vaccines of requisite antigenicity and avirulence for the prevention of influenza in man. 2) To continue our efforts to isolate and characterize the polypeptide antigens of the influenza viruses. 3) To study mechanisms of influenza virus virulence (and attenuation of virulence) through the comparative study of recombinant viruses with defined markers in a relative homogeneous host cell system with defined properties (clone 1- 5C-4 human aneuploid cells). 4) To continue studies of antigenic hybridization of influenza viruses as an approach to defining the permutations and limits of antigenic variation. 5) To investigate the role of the viral enzyme neuraminidase in influenza virus infection and immunity. 6) To continue general studies of influenza virus genetics by assessment of strain variation and transfer of strain characteristics by genetic recombination and complementation studies of conditional lethal mutants.